Radical vulvectomy and bilateral inguinal-femoral lymphadenectomy through separate incisions-experience with 100 cases.

Over a 6-year period 100 patients with vulvar cancer were treated by radical vulvectomy and bilateral inguinal femoral lymphadenectomy performed through separate incisions. The average age of the patients was 68.8 years. Ninety patients had squamous carcinoma, six had melanoma and four had other vulvar malignancies. FIGO staging was stage 1-46, stage II-25, and stage III-23, and stage IVa-6. Twenty-seven patients were found to have spread of tumor to groin nodes, 21 unilateral and six bilateral. For patients with squamous carcinomas, groin nodes were positive in four of 45 (8.9%) with tumor diameter < 2 cm vs. 17 of 42 (40.5%) with tumors> 2 cm. In 60 patients with unilateral squamous tumors, no isolated contralateral node metastases were found, however two of 13 patients (15.4%) with positive ipsilateral nodes had positive contralateral nodes also. One patient with negative nodes developed bilateral recurrent tumor in the skin bridges and subsequently died. Overall 5-year survival corrected for death from intercurrent illness was 74.6%. Corrected survival by stage for squamous carcinomas was as follows: stage I-96.7%, stage II-85%, stage III-45.8% and stage IV-50%.

The impact of loop diathermy on management of early invasive cervical cancer.

Large loop excision of the transformation zone (LLETZ) allows complete histologic assessment of cervical neoplasia. However, selective colposcopically directed punch biopsy followed by local ablation allows the possibility of inappropriate local ablation of early invasive lesions missed at punch biopsy. The onus of accurate diagnosis lies on the colposcopist. We have studied 1143 patients managed with loop diathermy and identified 35 invasive squamous carcinomas and 9 invasive adenocarcinomas. The data show that the cut-off for accurate colposcopic detection of invasive squamous lesions is not breach of the basement membrane but invasion up to a depth of 1 mm. On the other hand, colposcopy is an unreliable guide for the diagnosis of early adenocarcinoma. Diagnosis based on loop excision allows accurate, rational individualization of management for the unexpected diagnosis of colposcopically occult early invasive disease whilst retaining the logistic benefits of a 'see and treat' policy.

Simultaneous sampling of the endocervix and ectocervix using the profile brush.

In a controlled trial a new modified nylon brush (Profile brush) was compared for endocervical cell pickup with the combination of an Ayre spatula and traditional cytobrush. The two devices produced the same endocervical cell pickup rates (Ayre + cytobrush, 82.0%; Profile, 82.7%). The smears were of good quality, with no difference in the incidence of scanty or unsatisfactory smears. The Profile brush was easy to use. It may be an alternative to the combination of an Ayre spatula and cytobrush for sampling the cervix.

A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: a National Cancer Institute of Canada Clinical Trials Group Study.

OBJECTIVE: BAY 12-9566 (tanomastat) is a biphenyl matrix metalloprotease inhibitor (MMPI) with antiangiogenic and antimetastatic properties in vivo. The objective of the study was to determine whether the addition of BAY 12-9566 after optimal response to chemotherapy could improve time to progression (TTP). PATIENTS AND METHODS: Patients enrolled in the study had received 6-9 cycles of platinum/paclitaxel containing chemotherapy for stage III or IV ovarian carcinoma, with a response of no evidence of disease, or complete or partial response with residual disease < 2 cm. Patients were then randomized to BAY 12-9566 800 mg p.o. b.i.d. or placebo. The primary endpoint was progression-free survival (PFS); secondary endpoints were quality of life, toxicity, changes in CA 125 levels, response, and overall survival (OS). The total planned sample size was 730. RESULTS: The study was closed after 243 patients had been randomized because of Bayer's decision to close all ongoing trials due to negative results from other phase III trials in pancreatic and small cell lung cancer. The final analysis was performed in August 2000 after the requisite number of events for the first planned interim analysis had occurred; 54% of patients had progressed and 18% had died. PATIENT CHARACTERISTICS: performance status was ECOG 0/1/2 in 65/33/2%; median age 57 years; 79% of patients were FIGO stage III; 41% were optimally debulked; 76% had serous histology, and 67% had > or = grade 3 histology. Toxicity was generally grade 1 or 2 in severity, with the most common (BAY 12-9566 vs. placebo) being nausea (26% vs. 13%), fatigue (24% vs. 12%), diarrhea (14% vs. 10%), rash (12% vs. 7%), grade 3/4 thrombocytopenia (3% vs. 1%), and grade 3/4 anemia (5% vs. 1%). Median time to progression (TTP) was 10.4 months (8.5-11.5) for BAY 12-9566 and 9.2 months (7.2-13.9) for placebo (P = 0.67). Median overall survival (OS) was 13.9 months (12.9-infinity) for BAY 12-9566 and 11.9 months (10.5-16.5) for placebo (P = 0.53). CONCLUSION: We conclude that BAY 12-9566 was generally well tolerated and at the time of the final analysis, there was no evidence of an impact of BAY 12-9566 on PFS or OS.

Steroid modulation of pregnenolone to progesterone conversion by human placental cells in vitro.

Studies were performed to examine the production of progesterone by human placental cells in vitro. Samples of placentas from 22 women at term after spontaneous onset of labor and vaginal delivery were utilized. The tissue was dispersed into isolated cells with the use of collagenase, and suspensions of these cells were incubated with pregnenolone as substrate in the presence or absence of other compounds which may regulate progesterone production. These cell preparations produced progesterone in a dose-related fashion with exogenous pregnenolone. The conversion of pregnenolone to progesterone occurred rapidly, with most of the conversion completed during the first hour of incubation. The conversion was inhibited by dehydroepiandrosterone, estrone, androstenedione, and testosterone (p less than 0.001 in all cases). The inhibitory effect of androstenedione and testosterone was not dependent on aromatization to estrogen. Dihydrotestosterone and 5 alpha-pregnanedione resulted in a significant increase in the amount of progesterone present (p less than 0.001). In preliminary experiments, gonadotropin-releasing hormone, salbutamol, and propranolol were without significant effect in this system. We conclude that this system is a useful model for studying progesterone production by human placental tissue, and that placental progesterone production may be significantly influenced by the presence of other steroid hormones.

Effectiveness of letters to Cape Breton women who have not had a recent Pap smear.

Nova Scotia, and especially Cape Breton, has high cervical cancer incidence and mortality rates. Letters were sent to 15,691 unscreened and 6,995 under-screened women from Cape Breton Island encouraging them to obtain a Pap test. Controls were 61,510 unscreened women and 32,996 under- screened women in mainland Nova Scotia who were not sent letters. For this cohort study, the provincial Health Card Number database and Provincial Cytology Registry were linked. Having a Pap smear was associated with having received a letter (OR = 1.64), having been previously under-screened rather than unscreened (OR = 1.85), with youth and with higher income (OR = 1.13). After receiving a letter, women in Aboriginal, Mixed Black, Acadian, and rural communities had smear rates similar to those of other women. Being previously unscreened, rather than under-screened, was associated with higher rates of abnormalities (OR = 1.62), indicating greater need for early detection and treatment to prevent invasive cancer. While one-time letters to women improved the Pap smear screening rates, multiple, continuous interventions are needed to make a more substantive improvement in these rates.

Prognostic value of peritoneal cytology in endometrial carcinoma.

To determine whether positive peritoneal cytology is an independent poor prognostic factor in patients with endometrial carcinoma the records of 381 patients were reviewed. Positive peritoneal cytology was found in 24 of 381 (6.3%) patients. In clinical stage I disease, 16 of 322 (5.0%) patients had positive peritoneal cytology. Patients with positive cytology were more likely to have higher-grade tumors and extrauterine disease at the time of surgery (45% vs 2.3%) than were patients with negative cytology. Five-year survival was significantly less for patients with positive cytology than negative (50% vs 81.2%). For patients with surgical stage I disease (no extrauterine spread at surgery) there was no significant difference in 5-year survival between groups with positive and negative cytology (80% vs 86.3%). The majority (70.8%) of patients with endometrial cancer and positive peritoneal cytology have extrauterine disease at the time of surgery. Although overall 5-year survival is less for patients with positive cytology, when other risk factors are controlled for, there is no difference in survival for patients with no demonstrable extrauterine disease despite positive cytology. We conclude that positive peritoneal cytology is not an independent prognostic indicator for patients with endometrial cancer.